There is rich clinical evidence that observing normally executed actions promotes the recovery of the corresponding action execution in patients with motor deficits. In this study, we assessed the ...ability of action observation to prevent the decay of healthy individuals' motor abilities following upper-limb immobilization. To this end, upper-limb kinematics was recorded in healthy participants while they performed three reach-to-grasp movements before immobilization and the same movements after 16 h of immobilization. The participants were subdivided into two groups; the experimental group observed, during the immobilization, the same reach-to-grasp movements they had performed before immobilization, whereas the control group observed natural scenarios. After bandage removal, motor impairment in performing reach-to-grasp movements was milder in the experimental group. These findings support the hypothesis that action observation, via the mirror mechanism, plays a protective role against the decline of motor performance induced by limb nonuse. From this perspective, action observation therapy is a promising tool for anticipating rehabilitation onset in clinical conditions involving limb nonuse, thus reducing the burden of further rehabilitation.
To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema ...(DME).
Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.
Six hundred sixty-six patients with DME.
An independent reading center measured the area of RNP on fluorescein angiograms obtained in the phase 3 RISE and RIDE trials.
The percentage of patients with no posterior RNP.
The percentage of patients with no posterior RNP decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. After month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. The percentage of patients who showed an increase in posterior RNP from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6% vs. 18.5%; P = 0.016) and 24 (16.1% vs. 37.6%; P<0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3% vs. 23.0%; P = 0.013) through 24 (15.0% vs. 37.6%; P<0.0001) for ranibizumab 0.3 mg. Initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior RNP from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise.
Just as high VEGF levels contribute to progression of retinal nonperfusion in retinal vein occlusion, the same is true in patients with DME, suggesting that regardless of the underlying disease process, high levels of VEGF can cause closure of retinal vessels. However, our data also suggest that VEGF-induced worsening of retinal perfusion in DME is superimposed on another cause of more gradually worsening perfusion, possibly glucotoxicity. Thus, monthly injections of ranibizumab can slow, but not completely prevent, retinal capillary closure in patients with DME.
The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema DME and proliferative diabetic retinopathy PDR), which require ...frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR.
Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom.
Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease.
A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study ETDRS and ultra-widefield UWF fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists).
Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings.
The new pathway showed sensitivity of 97% (95% confidence interval CI, 92%–99%) and specificity of 31% (95% CI, 23%–40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% 95% CI, 77%–91% and 48% 95% CI, 41%–56%, respectively) or UWF images (83% 95% CI, 75%–89% and 54% 95% CI, 46%–61%, respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% 95% CI, 78%–93% and 49% 95% CI, 42%–56%, respectively, for UWF versus 80% 95% CI, 69–88% and 40% 95% CI, 34%–47%, respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits.
The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.
Background. Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. We describe the detection of circulating Mucorales DNA (cmDNA) for the ...early diagnosis of IWM in those patients and report the potential value of detecting cmDNA for treatment guidance. Methods. Severely ill burn patients admitted to our tertiary referral center between October 2013 and February 2016 were included. Retrospective plasma samples were tested for the presence of cmDNA by quantitative real-time polymerase chain reaction (qPCR). Patients were then prospectively screened twice a week, and liposomal amphotericin-B therapy initiated based on a positive qPCR. The primary endpoint was the time between cmDNA detection and standard diagnosis. Secondary endpoints were the time from cmDNA detection and treatment initiation and mortality. Results. Seventy-seven patients (418 samples) were included. The average age was 46 (28–60) years, abbreviated burn severity index was 8 (7–10), and simplified acute physiology score was 33 (23–46). The total body surface area was 33% (22%–52%). cmDNA was detected 11 (4.5–15) days before standard diagnosis. The in-hospital mortality was 62% for patients with IWM and 24% for those without (P = .03). The mortality due to IWM was 80% during period A and 33% during period B (P = .46). Conclusions. This study suggests that the detection of cmDNA allows earlier diagnosis of IWM in severely ill burn patients and earlier initiation of treatment. Further studies are needed to confirm the impact of earlier treatment initiation on patient outcome.
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Sepsis, the most common cause of admission to an intensive care unit (ICU), has had an increased incidence and prevalence over the last years with a simultaneous decrease in its short-term mortality. ...Sepsis survivors are more frequently discharged from hospital and often experience long-term outcomes such as late mortality, immune dysfunction, secondary infections, impaired quality of life, and unplanned readmissions. Early recognition and management of sepsis have challenged emergency care and critical care physicians and nurses. New sepsis definitions were produced and the Surviving Sepsis Campaign (SSC) 2016 was updated recently. Although hospital readmissions after sepsis are common, associated risk factors and how to manage patients who survive an episode of sepsis still need clarification. The immune dysfunction caused by sepsis/septic shock is complex, persistent, affects inflammatory and anti-inflammatory systems, and might be associated with long-term outcomes of sepsis. Several randomized controlled trials (RCT) that analyzed new (and old) interventions in sepsis/septic shock are discussed in this review in parallel with the SSC 2016 recommendations and other guidelines when relevant. RCTs addressing incidence, treatment, and prevention of important sepsis-associated organ dysfunction such as the acute respiratory distress syndrome, acute kidney injury, and brain dysfunction are highlighted. Finally, we briefly discuss the need for novel targets, predictive biomarkers, and new designs of RCTs in sepsis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Nevus of Ota (NO), also known as "brownish-blue nevus of the palate of the eye", is a benign dermal pigmentation that increases skin disease. The Q-switched ruby laser is a classic treatment for ...nevus of Ota in children, but the optimal age for treatment is still controversial. The aim of this study was to investigate the treatment effect of Q-switched ruby laser in children with nevus of Ota at different ages and the effect on psychological health status.Background and ObjectiveNevus of Ota (NO), also known as "brownish-blue nevus of the palate of the eye", is a benign dermal pigmentation that increases skin disease. The Q-switched ruby laser is a classic treatment for nevus of Ota in children, but the optimal age for treatment is still controversial. The aim of this study was to investigate the treatment effect of Q-switched ruby laser in children with nevus of Ota at different ages and the effect on psychological health status.Children with nevus of Ota treated with Q-switched ruby laser in the Department of Dermatology of the Second Affiliated Hospital of Wenzhou Medical University from June 2015 to June 2019 were retrospectively analysed. And the mental health status was assessed using the CDI scale.Materials and MethodsChildren with nevus of Ota treated with Q-switched ruby laser in the Department of Dermatology of the Second Affiliated Hospital of Wenzhou Medical University from June 2015 to June 2019 were retrospectively analysed. And the mental health status was assessed using the CDI scale.In the preschool children group (0-7 year age), the significant efficacy rates was 93.1%, the average number of treatments was 3.6, and the overall incidence of adverse reactions was 4.7%. The significant efficacy rates in the school-age children group (7-14 year age) was 90.3%, the average number of treatments was 5.1, and the overall incidence of adverse reactions was 13.7%. The mean post-treatment CDI score in the preschool children group was 10.8, and 9.7% of children exceeding 19 points. The mean pre-treatment CDI score in the school-age children group was 17.3, and 24.6% of children exceeding 19 points. The mean post-treatment CDI score was 13.6 and 15.1% of children exceeded 19 points. The chi-square test for the significant efficacy rate of the two groups showed P>0.05, which was not statistically significant. The significant efficacy rate of the preschool group and that of the school-age children group. The t-test for the number of treatments in the two groups showed P<0.05, which was statistically significant. Adverse reactions in the two groups showed a statistically significant P<0.05. The mean CDI scores and the percentage of depressed individuals in the school-age children group were significantly lower after treatment than before treatment (p<0.05).ResultsIn the preschool children group (0-7 year age), the significant efficacy rates was 93.1%, the average number of treatments was 3.6, and the overall incidence of adverse reactions was 4.7%. The significant efficacy rates in the school-age children group (7-14 year age) was 90.3%, the average number of treatments was 5.1, and the overall incidence of adverse reactions was 13.7%. The mean post-treatment CDI score in the preschool children group was 10.8, and 9.7% of children exceeding 19 points. The mean pre-treatment CDI score in the school-age children group was 17.3, and 24.6% of children exceeding 19 points. The mean post-treatment CDI score was 13.6 and 15.1% of children exceeded 19 points. The chi-square test for the significant efficacy rate of the two groups showed P>0.05, which was not statistically significant. The significant efficacy rate of the preschool group and that of the school-age children group. The t-test for the number of treatments in the two groups showed P<0.05, which was statistically significant. Adverse reactions in the two groups showed a statistically significant P<0.05. The mean CDI scores and the percentage of depressed individuals in the school-age children group were significantly lower after treatment than before treatment (p<0.05).Q-switched ruby laser is safe and effective in treating nevus of Ota in children. Early treatment can reduce the number of treatments and the incidence of adverse reactions. In addition, early treatment can reduce children's depression, which is beneficial to mental health.ConclusionQ-switched ruby laser is safe and effective in treating nevus of Ota in children. Early treatment can reduce the number of treatments and the incidence of adverse reactions. In addition, early treatment can reduce children's depression, which is beneficial to mental health.
Water contamination by pharmaceuticals is a global concern due to their potential negative effects on aquatic ecosystems and human health. This study examined the presence of three repositioned drugs ...used for COVID-19 treatment: azithromycin (AZI), ivermectin (IVE) and hydroxychloroquine (HCQ) in water samples collected from three urban rivers in Curitiba, Brazil, during August and September 2020. We conducted a risk assessment and evaluated the individual (0, 2, 4, 20, 100 and 200 μg.L−1) and combined (mix of the drugs at 2 μg.L−1) effects of the antimicrobials on the cyanobacterium Synechococcus elongatus and microalga Chlorella vulgaris. The liquid chromatography coupled to mass spectrometry results showed that AZI and IVE were present in all collected samples, while HCQ occurred in 78 % of them. In all the studied sites, the concentrations found of AZI (up to 2.85 μg.L−1) and HCQ (up to 2.97 μg.L−1) represent environmental risks for the studied species, while IVE (up to 3.2 μg.L−1) was a risk only for Chlorella vulgaris. The hazard quotients (HQ) indices demonstrated that the microalga was less sensitive to the drugs than the cyanobacteria. HCQ and IVE had the highest values of HQ for the cyanobacteria and microalga, respectively, being the most toxic drugs for each species. Interactive effects of drugs were observed on growth, photosynthesis and antioxidant activity. The treatment with AZI + IVE resulted in cyanobacteria death, while exposure to the mixture of all three drugs led to decreased growth and photosynthesis in the cells. On the other hand, no effect on growth was observed for C. vulgaris, although photosynthesis has been negatively affected by all treatments. The use of AZI, IVE and HCQ for COVID-19 treatment may have generated surface water contamination, which could increased their potential ecotoxicological effects. This raises the need to further investigation into their effects on aquatic ecosystems.
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•Concomitant concentrations of AZI, IVE and HCQ were found in urban rivers.•At the found concentrations, AZI and HCQ represent risks to S. elongatus and C. vulgaris.•AZI, IVE and HCQ show integrative effects.•Individual toxic effects were amplified by the pharmaceutical mixture.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
OBJECTIVEThe aim of this study was to evaluate referral and treatment delays by ethnicity/race in patients with rheumatoid arthritis (RA) treated at an academic rheumatology center.
METHODSWe ...reviewed the medical records of all RA patients evaluated at an outpatient clinic between 2011 and 2016 to identify newly diagnosed and naive-to-treatment patients. We determined the durations between symptom onset and first rheumatology visit and time to initiate treatment. Data extraction included referral source, demographics, treatment, and laboratory tests. Routine use of a multidimensional health assessment questionnaire allowed us to calculate baseline RAPID3 (routine assessment of patient index data 3) scores. Comparisons between self-reported ethnicity/race groups were performed. We used logistic regression models to analyze associations between baseline variables and early referral.
RESULTSData from 152 disease-modifying antirheumatic drug-naive RA patients were included in the study; 35% were white, 37% black, 20% Hispanic, and 8% other. The range in median time to first rheumatology visit was 6 to 8 months for all patient groups, except Hispanic. This group had a median time of 22.7 months (p = 0.01). The referral pattern was considerably variable between-groups; 40% of Hispanic patients were self-referred (p = 0.01). There were no statistically significant between-group differences for time to treatment initiation according to ethnicity/race. RAPID3 scores (p = 0.04) and erythrocyte sedimentation rates (p = 0.01) were significantly higher in the black and Hispanic groups. A high C-reactive protein value at baseline was associated with earlier referral.
CONCLUSIONSThere is significant delay in initial presentation to a rheumatologist that was associated with a higher disease severity at presentation, especially for Hispanic patients.
Since the start of the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) pandemic, several treatments have been proposed to cure coronavirus disease 2019 (COVID‐19) and prevent it. ...Molnupiravir is a ribonucleoside prodrug of N‐hydroxycytidine with an in vitro and in vivo activity against SARS‐CoV‐2. We conducted a retrospective cohort study that included all people treated with molnupiravir between January 10, 2022, and March 31, 2022, at the University Hospital of Sassari. Molnupiravir was prescribed, according to the Italian Agency of Drug indications, to patients with recent symptom onset (≤5 days), no need for oxygen supplementation, and with a high risk of disease progression for the presence of chronic diseases. We included 192 people with a mean age of 70.4 ± 15.4 years, with 144 (75%) patients over 60 years. During the follow‐up, 20 (10.4%) patients showed a disease progression. At the multivariate analysis, older age, having neurological disease, having dyspnea at the onset of the symptoms, and acquiring SARS‐CoV‐2 infection during hospital admission were associated with an increased risk of progression. In contrast, an early start of treatment was associated with a reduced risk of disease progression. Molnupiravir was also extremely safe since 13 (6.8%) adverse events were reported, with only one interruption. Our study shows that monlupiravir confirmed its efficacy and safety in a real‐life cohort that included a high percentage of elderly people with a high comorbidity burden.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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